Fast Heating of Imploded Core with Counterbeam Configuration.

A tailored-pulse-imploded core with a diameter of 70 µm is flashed by counterirradiating 110 fs, 7 TW laser pulses. Photon emission (>40 eV) from the core exceeds the emission from the imploded core by 6 times, even though the heating pulse energies are only one seventh of the implosion energy. The coupling efficiency from the heating laser to the core using counterirradiation is 14% from the enhancement of photon emission. Neutrons are also produced by counterpropagating fast deuterons accelerated by the photon pressure of the heating pulses. A collisional two-dimensional particle-in-cell simulation reveals that the collisionless two counterpropagating fast-electron currents induce mega-Gauss magnetic filaments in the center of the core due to the Weibel instability. The counterpropagating fast-electron currents are absolutely unstable and independent of the core density and resistivity. Fast electrons with energy below a few MeV are trapped by these filaments in the core region, inducing an additional coupling. This might lead to the observed bright photon emissions.

Direct heating of a laser-imploded core by ultraintense laser-driven ions.

A novel direct core heating fusion process is introduced, in which a preimploded core is predominantly heated by energetic ions driven by LFEX, an extremely energetic ultrashort pulse laser. Consequently, we have observed the D(d,n)^{3}He-reacted neutrons (DD beam-fusion neutrons) with the yield of 5×10^{8} n/4π sr. Examination of the beam-fusion neutrons verified that the ions directly collide with the core plasma. While the hot electrons heat the whole core volume, the energetic ions deposit their energies locally in the core, forming hot spots for fuel ignition. As evidenced in the spectrum, the process simultaneously excited thermal neutrons with the yield of 6×10^{7} n/4π sr, raising the local core temperature from 0.8 to 1.8 keV. A one-dimensional hydrocode STAR 1D explains the shell implosion dynamics including the beam fusion and thermal fusion initiated by fast deuterons and carbon ions. A two-dimensional collisional particle-in-cell code predicts the core heating due to resistive processes driven by hot electrons, and also the generation of fast ions, which could be an additional heating source when they reach the core. Since the core density is limited to 2 g/cm^{3} in the current experiment, neither hot electrons nor fast ions can efficiently deposit their energy and the neutron yield remains low. In future work, we will achieve the higher core density (>10 g/cm^{3}); then hot electrons could contribute more to the core heating via drag heating. Together with hot electrons, the ion contribution to fast ignition is indispensable for realizing high-gain fusion. By virtue of its core heating and ignition, the proposed scheme can potentially achieve high gain fusion.

Performance of a rapid human metapneumovirus antigen test during an outbreak in a long-term care facility.

Using a newly developed rapid test, an outbreak of human metapneumovirus (HMPV) infection in a long-term care facility was detected within only 2 days after the onset of symptoms in a putative index case. The outbreak was almost under control within 8 days mainly by zoning patients, with the exception of two cases of HMPV that were diagnosed 16 and 17 days after the onset of the outbreak. According to an immunological diagnosis as well as the rapid test, it was eventually proven that 18 patients had HMPV infections. We suspected that even asymptomatic residents, who had not been completely separated from the facility population, were a source of infection. That suggested that all asymptomatic residents should be tested and that the separation of the infected patients should be absolute, if an outbreak of HMPV infection is suspected in such a facility.

Fusion using fast heating of a compactly imploded CD core.

A compact fast core heating experiment is described. A 4-J 0.4-ns output of a laser-diode-pumped high-repetition laser HAMA is divided into four beams, two of which counterilluminate double-deuterated polystyrene foils separated by 100 µm for implosion. The remaining two beams, compressed to 110 fs for fast heating, illuminate the same paths. Hot electrons produced by the heating pulses heat the imploded core, emitting x-ray radiations >20 eV and yielding some 10(3) thermal neutrons.

Primary structure of scombrine gamma, protamine isolated from spotted mackerel (Scomber australasicus).

Spotted mackerel protamine, scombrine, was isolated from the sperm of a spotted mackerel (Scomber australasicus) by extraction with sulfuric acid and fractionated into one major (scombrine II) and one minor (scombrine I) components by chromatography on CM-Sephadex C-25. Scombrine II gave a single band, whereas scombrine I gave three bands upon PAGE. Scombrine II (scombrine gamma) consists of 34 amino acid residues, and its sequence is: Pro-Arg-Arg-Arg-Arg-Arg-Ala-Ser-Arg-Pro-Val-Arg-Arg-Arg-Arg-Arg- Ala-Arg-Arg-Ser-Thr-Ala-Val-Arg-Arg-Arg-Arg-Arg-Val-Val-Arg-Arg-Arg-Arg. The ion spray mass spectrum shows that scombrine gamma has a molecular mass of 4,532.13 Da. The other minor component (scombrine I) is considered to be a mixture of degradation products of scombrine gamma based on the results of PAGE and ion spray mass spectrometry. Scombrine gamma has a similar sequence to sardaine Z2 from striped bonito except for two positions.

Primary structures of sardaines Z1 and Z2, protamines isolated from striped bonito (Sarda orientalis).

Striped bonito protamine, sardaine, was isolated from the sperm of striped bonito (Sarda orientalis) by extraction with sulfuric acid followed by ion-exchange chromatography. The preparation gave a single band upon polyacrylamide gel electrophoresis. Sardaine consists of 34 amino acid residues, and its sequence is: Pro-Arg-Arg-Arg-Arg-Arg-Ser(Ala)-Ser-Arg-Pro-Val-Arg-Arg-Arg-Arg-Arg-Tyr -Arg- Arg-Ser-Thr-Ala-Ala-Arg-Arg-Arg-Arg-Arg-Val-Val-Arg-Arg-Arg-Arg. At position 7, serine (sardaine Z1) is partially replaced by alanine (sardaine Z2). The ion spray mass spectrum shows that sardaines Z1 and Z2 have molecular masses of 4,612.49 and 4,596.09 Da, respectively. The sequence of sardaine Z1 is 100% identical with that of thynnine Z2 from tuna fish (both fish belong to Scombridae, Perciformes).

Detection of cytomegalovirus DNA in urine from newborns in NICU using a polymerase chain reaction.

To investigate the natural course of viral shedding during the newborn period, the presence of Cytomegalovirus (CMV) DNA in specimens at 3, 7, 14, 21 and 28 days of life was examined using the polymerase chain reaction (PCR) method. At the 3rd day of life, the viral DNA positive rate in the urine was 7% (4/60), at the 7th day 7% (3/46), at the 14th day 10% (2/20), at the 21st day 10% (1/10), and at the 28th day 25% (1/5). CMV was also detected in samples co-cultivated with HeLa 229 cells and this positive rate was 5% (3/60). The viral positive rate in newborns did not correlate with the gestational age, body weight, or serum IgM level. Six congenital infection cases were identified; two of which were small-for-date babies (SFD) and three of which were born with premature rupture of membranes (PROM). They had no complications during the six months after birth.

[Plasmodium falciparum infection in a 8-year old boy].

A 8-year old Japanese boy who returned from Tanzania was admitted to our hospital because of fever, vomiting, and headache. He was diagnosed as a Plasmodium falciparum infection verified by a blood smear. He was treated with quinine and halofantrine, and recovered completely. Malaria infection should be considered when patients return from Malaria endemic areas.

[A child with iritis due to Chlamydia pneumoniae infection].

A case of uncommon iritis due to Chlamydia pneumoniae (C. pneumoniae) is reported. The patient was a 9-year-old boy who had suffered from cough, pharyngeal pain, and low grade fever. The symptoms persisted for more than 1 month in spite of an oral cephem antibiotic. Ophthalmalgia, congestion around the iris and cough had lasted with alleviation and exacerbation. A diagnosis of C. pneumoniae infection was made by specific polymerase chain reaction (PCR) method and microimmunofluorescence test (MIF). The symptoms subsided with administration of clarithromycin (CAM: 300 mg/day) for 2 weeks. Because of the simultaneous alleviation of iritis, C. pneumoniae infection was considered to introduce the iritis. Much remains to be clarified about this pathogenesis of iritis and more detailed evaluations are required.

[Alpha-hemolytic streptococcal septicemia and meningitis in immunocompromised children].

Many kinds of microorganisms can produce toxic septicemia in immunocompromised hosts. We are reporting alpha-hemolytic streptococcal septicemia and meningitis in two children with hematological malignancies. [Case 1] 6 year old girl who had been suffering from acute lymphocytic leukemia. She had sepsis and bacterial meningitis in maintenance-therapy for leukemia. Streptococcus sanguis was isolated from the blood and cerebrospinal fluid (CSF). [Case 2] 11 year old girl who had had malignant lymphoma (non-Hodgkin type). She also had sepsis and bacterial meningitis due to Streptococcus mitis which was isolated from blood and CSF in maintenance-therapy. Both cases had been treated with anti-cancer drugs and had severe granulocytopenia. Positive rate of blood cultures during the recent 6 years (1984.1-1989.12) at our department was 6.0% (total number of cultures were 2,019, positive cultures were 121). Strains of 131 bacteria were determined; Gram-positive cocci were 70 strains (53.4%) and Gram-negative rods were 52 strains (39.7%). Fifteen strains (11.5%) of alpha-hemolytic Streptococci were isolated during 6 years. One hundred thirteen cases of septicemia were analysed in medical charts and 12 cases of alpha-hemolytic streptococcal septicemia were observed (5 cases with infective endocarditis and 7 cases in immunocompromised states).

[Severe infections due to Streptococcus milleri in children].

Streptococcus milleri (S. milleri) is found in healthy individuals in the mouth, nasopharynx, throat, vagina and in feces, and has been reported to be isolated from several infectious diseases in man, particularly from abscess in various parts of the body. We report two cases of severe infections due to S. milleri isolated from subdural abscess and pleural empyema. [Case 1] 13 year old boy who had been healthy until he was noticed to have meningeal signs and was diagnosed as left subdural abscess with siagonantritis by cranial CT scans. S. milleri was isolated from subdural abscess and maxillary sinus. [Case 2] 10 year old boy who had encephalitis and severe mental retardation after measles at 6 months of age. He had a fever, dyspnea and chest X-ray abnormalities and was diagnosed as right pleural empyema. Three strains of organism, S milleri, Bacteroides spp. and Fusobacterium nucleatum were isolated from the pleural effusion.

Serotypes of human rotaviruses in 7 regions of Japan from 1984 to 1997.

Human rotavirus (HRV) serotypes were studied from diarrheal stool specimens in children in 7 regions of Japan (Sapporo, Tokyo, Maizuru, Osaka, Kagawa, Kurume, and Saga) from 1984 to 1997 by enzyme immunoassay (EIA) with serotype-specific monoclonal antibodies against serotypes 1, 2, 3, and 4. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was conducted for analysis of "others" which included nonserotypable and mixed-serotype rotavirus specimens by EIA. In 3756 rotavirus-positive specimens, serotype 1 was detected in 2649 (70.5%), serotype 2 in 362 (9.6%), serotype 3 in 232 (6.2%) and serotype 4 in 196 (5.2%). Overall, serotype 1 was predominant from 1984 to 1997, although there were a few cases in which serotype 2, 3 and 4 became predominant based on area and year. The frequency of serotype 1 has gradually increased since 1993. Twenty two, 2, 3 and 1 among 57 specimens of "others" by EIA from Tokyo, Maizuru, Sapporo and Kurume in 1995-1996 and 1996-1997 were determined as serotypes 1, 2, 3, and 9 by RT-PCR, respectively.

Nedaplatin and 5-FU combined with radiation in the treatment for esophageal cancer.

A series of patients with esophageal cancer was treated with chemotherapeutic regimens of the new antitumor platinum preparation nedaplatin plus 5-FU in combination with radiation therapy, and the therapeutic responses, side effects, and complications were clinically assessed. There were 2 patients with a complete response and 11 patients with a partial response, hence, a response rate of 76.5%. Major adverse reactions were those of hematological toxicity and included leukopenia (13 patients, 76.5%), thrombocytopenia (8 patients, 47.1%), and lowered serum hemoglobin concentration (9 patients, 52.9%). The leukopenia and thrombocytopenia, though of a grade 3 severity in 3 and 2 patients, respectively, subsided spontaneously in all affected cases. Gastrointestinal adverse reactions were mild and included appetite loss in 7 patients (41.2%) and nausea in 2 patients (11.8%). The only abnormality in renal function observed was a slight elevation of serum creatinine in one patient. The combined therapy of chemotherapy with nedaplatin and 5-FU plus radiation produced a high response rate in the treatment of carcinoma of the esophagus and was associated with reduced gastrointestinal and renal toxicity. The results indicate the combined therapy with nedaplatin to be clinically useful.

[A pharmacokinetic investigation of sisomicin administered intramuscularly to children].

For the purpose of studying the pharmacokinetic profile of sisomicin (SISO) and the proper conditions for its administration to children, SISO was administered intramuscularly to 10 infants aged less than 1 year, 16 young children and 18 school children at doses of 1.0, 1.5 and 2.0 mg/kg and its serum and urine levels were determined by bioassay. The mean peak levels of SISO in serum appeared at 1/4 hour in the infants, irrespective of the dose; the mean peak levels were 2.27, 3.05 and 4.83 micrograms/ml after the 1.0, 1.5 and 2.0 mg/kg doses, respectively. In the young children, the mean peak levels appeared at 1/4 hour after the 1.0 mg/kg dose and at 1/2 hour after both the 1.5 mg/kg and 2.0 mg/kg doses. The mean peak levels were 2.82, 3.80 and 6.43 micrograms/ml, respectively. In the school children, the mean peak levels appeared at 1/2 hour after all the doses and were 4.34, 5.31 and 6.87 micrograms/ml, respectively. The mean peak levels were in the order of school children greater than young children greater than infants and were dose-dependent. In the infants, the mean urinary recovery was 43.7% for the 1.0 mg/kg dose and 31.2% for the 1.5 mg/kg dose; in the young children, 50.5, 35.9 and 65.6% for the 1.0, 1.5 and 2.0 mg/kg doses, respectively; and in the school children, 54.2, 50.2 and 56.7%. Using the observed serum levels, the pharmacokinetic parameters were calculated according to the one-compartment open model theory. (1) The mean elimination rate constants (K) were calculated at 0.60, 0.67 and 0.56 hr-1 for the infants, young children and school children, respectively. There were found no great differences among the above 3 age groups. The mean absorption rate constants (ka) were 18.5, 7.6 and 5.9 hr-1 and the apparent volumes of distribution per kg body weight, Vd (L/kg), 0.44, 0.26 and 0.22 L/kg, respectively. These 2 parameters were significantly greater in the infants than in the young children and school children. The maximum serum concentration (Cmax) and the time when the concentration reaches a maximum (Tmax) were substantially in agreement with the observed values. The half-lives (T1/2) were 1.16, 1.03 and 1.23 hours for infants, young children and school children, respectively, and did not differ significantly among the 3 groups. A serum level simulation curve constructed by plotting the mean values for K, ka and Vd did not reveal any substantial deviation from the observed values.(ABSTRACT TRUNCATED AT 400 WORDS)

[Clinical studies of PC-904 in pediatrics (author's transl)].

PC-904 was administered to 24 patients: urinary tract infections (7 cases), bronchitis (2 cases), pneumonia (3 cases), brain abscess (1 case), septicemia and the suspected cases (10 cases), and buttock abscess (1 case). The daily dosage varied from 60 to 223.4 mg/kg and averaged 86.9 mg/kg. The drug was administered three times a day by 1-hour drip infusion, and the duration of the treatment averaged 11 days. Clinical results were obtained as excellent responses in 5 cases, good in 13, poor in 4, and unknown in 2, giving 75% of the clinical effectiveness. Bacteriological responses were excellent in 7, good in 2, poor in 2, and unknown in 13, and the overall effectiveness was evaluated as excellent in 2, good in 17, and unknown in 5. Antibacterial activities against clinically isolated bacteria were examined. MIC values of PC-904 were over 100 mg/ml 1 strain of E. coli and 2 strains of Klebsiella, however excellent sensitivities were observed in 3 strains of Ps. aeruginosa and MIC values varied 1.56 to 3.12 microgram/ml at 10(8) of inoculum size and 0.78 to 1.56 microgram/ml at 10(8). As to side effects, diarrhea was observed in 1 case, rash in 2, lowering ob blood pressure in 2, elevation of GOT in 1, and elevation of LDH in 2. Abnormal elevations of GOT (10 cases), GPT (5 cases), A1-P (1 case), LDH (7 cases), and BUN (1 case) were noticed in other patients, but it was considered to be due to underlying diseases.

[Effect of BMY-28100 on bacterial flora in adult human feces].

We investigated effects of BMY-28100 on fecal bacteria. BMY-28100 was administered orally to 8 healthy male volunteers between 20 and 24 years of age weighing between 58.0 and 79.5 kg. All subjects were given one 250 mg capsule 3 times a day at 30 minutes after meal for 7 days. Fecal bacterial counts were examined 5 days before the start of administration, the day of the start of administration, 3, 5 and 7 days after the start of administration, and 3, 5, 10, 20 and 30 days after the end of administration. Concentrations of BMY-28100 and Clostridium difficile D-1 toxin in feces were also examined together with examinations for adverse reactions and abnormal laboratory test values. 1. Total aerobic bacterial counts increased transiently upon the antibiotic dosage. Escherichia coli and yeast like organism increased transiently during the period of administration, while the total counts of anaerobic bacteria remained constant. Veillonellaceae, Peptococcaceae and Eubacterium decreased transiently during the period of administration. Although C. difficile and its D-1 toxin were detected in 1 and 5 cases, respectively, these feces appeared normal. 2. Active metabolites of BMY-28100 were not detected in the feces. 3. No adverse effects or no abnormal laboratory test values were observed.

[Basic and clinical studies on S-1108 in pediatric field].

S-1108 is a new oral esterified cephem antibiotic. Its active form, S-1006, has a broad antimicrobial spectrum against both Gram-positive and Gram-negative bacteria. Furthermore, S-1006 is extremely stable against beta-lactamases with some exceptions. In the present study, we conducted laboratory and clinical evaluations of S-1108 granules in pediatrics. The obtained results are summarized as follows. 1. A drug sensitivity test revealed that MIC80 of the drug against 456 clinical isolates of Staphylococcus aureus that had been kept in our laboratory was 6.25 micrograms/ml, similar to those of cefaclor (CCL) and methicillin (DMPPC). The most frequent MIC was 1.56 micrograms/ml against 20 strains of S. aureus isolated from patients who received this drug, and this value was similar to those for CCL, amoxicillin (AMPC) and DMPPC. As regards to Streptococcus pyogenes, MIC of S-1006 was < or = 0.025 microgram/ml against 449 clinical isolates in our culture collection and 7 strains obtained from patients who received this drug, and these MICs are similar to those of cefteram (CFTM). MICs of S-1006 against 5 strains of Streptococcus pneumoniae obtained from patients who received this drug were < or = 0.025 microgram/ml, 0.10 microgram/ml or 0.39 microgram/ml which are similar to those of CFTM. MICs of S-1006 against 4 strains of Haemophilus influenzae obtained from patients who received this drug were 0.05 or 0.10 microgram/ml which are similar to those of CFTM. 2. When S-1108 granule preparation was administered to 1 patient at 4.0 mg/kg, the peak plasma concentration of S-1006 was 1.25 microgram/ml. S-1108 granule preparation was also administered to 2 patients at 6.0 mg/kg, and the peak plasma concentrations were 2.43 micrograms/ml and 2.23 micrograms/ml. Plasma half-lives were 1.11 hours after 4.0 mg/kg and 1.28 hours in both patients given 6.0 micrograms/ml. AUCs were 4.06, 8.37 and 7.73 micrograms.hr/ml, respectively. A dose-response relationship was observed between the two doses. 3. Urinary concentration was the highest during the 4-6-hour period for a patient given 4.0 mg/kg, and during the 0-2-hour or 4-6-hour period for 2 patients given 6.0 mg/kg. The peak concentrations were 258.0, 602.0 and 500.0 micrograms/ml, respectively, and urinary recovery rates during the 0-8-hour period were 38.9, 38.3 and 23.1%, respectively. 4. Clinical effects were excellent or good in 88 of 93 patients, showing a very high efficacy rate of 94.6%.(ABSTRACT TRUNCATED AT 400 WORDS)

[Laboratory and clinical studies on flomoxef in neonates and premature infants].

Flomoxef (FMOX), an oxacephem antibiotic of beta-lactam antibiotic family, was administered to 16 infants including 6 neonates and 10 premature infants at a dose of 20 or 40 mg/kg via intravenous injection, and plasma and urinary concentrations and the urinary recovery were determined. In addition, FMOX was administered via intravenous injection at daily doses averaging 85.5 mg/kg divided into 2 to 4 times for durations averaging 9 days to 96 infants from 0- to 90-day old (mainly neonates and premature infants). In 44 of the 96 infants with bacterial infections, clinical and bacteriological efficacies were evaluated, and prophylactic effects of FMOX were determined in the remaining 52 infants. Adverse reaction and laboratory tests abnormalities were evaluated also. The obtained results are summarized as follows. 1. Upon administration of FMOX at 20 or 40 mg/kg to neonates and premature infants via intravenous injection, plasma concentrations, half-lives and AUC were determined. In 3 neonates of 5, 7 and 16 days of ages administered with 20 mg/kg of FMOX, peak plasma concentrations of 62.5 to 99.7 micrograms/ml were achieved in 5 or 15 minutes after injection. Half-lives of FMOX in these neonates were 1.48 to 1.78 hours and AUC's were 112 to 161 micrograms.hr/ml. The same dose (20 mg/kg) of FMOX was administered to 3 premature infants of 5- 16- and 19-day of ages and initial blood samples were obtained at 5 minutes after injection from the 5-day old subject and at 15 minutes after injection from the 16-and 19-day old subjects. Peak plasma concentrations of 63.6 to 79.9 micrograms/ml were observed in the samples. Half-lives were 1.69 to 2.20 hours and AUC's were 174 to 201 micrograms.hr/ml. When 3 neonates (one 17-day old and two 24-day old subjects) were administered with 40 mg/kg of FMOX, peak plasma concentrations obtained at 5 minutes after injection were 99.7 to 122.0 micrograms/ml. Half-lives were 1.28 to 1.92 hours and AUC's were 170 to 357 micrograms.hr/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

[Bacteriological, pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field].

Antibacterial activities were determined and pharmacokinetics and a clinical studies were performed on biapenem (L-627), a novel parenteral carbapenem antibiotic, in infections in children. The following results were obtained: 1. MICs of L-627 against clinical isolates were as follows: Among Gram-positive bacteria, MICs were 0.78 microgram/ml to > 100 micrograms/ml against 3 strains of methicillin-resistant Staphylococcus aureus (MRSA), and 0.10 microgram/ml to 0.39 microgram/ml against 8 strains of methicillin-sensitive S. aureus (MSSA), MICs against 5 of them were similar to those of imipenem (IPM), and MICs against 3 of them were slightly higher than those of IPM. MICs were < or = 0.025 microgram/ml to 0.39 microgram/ml against 7 strains of Streptococcus pneumoniae, and were similar to those of IPM, and lower than those of ceftazidime (CAZ) and piperacillin (PIPC). Among Gram-negative bacteria, MICs were 0.78 microgram/ml and 3.13 micrograms/ml against 2 strains of Haemophilus influenzae, and were similar to those of IPM. 2. Maximum plasma concentrations determined by the bioassay method after intravenous infusion of L-627 over 30 minutes at doses of 6.0 and 12.0 mg/kg, respectively, in 2 different pairs of 2 children each (total 4 cases) were observed upon completion of the treatment. Maximum concentrations at a dose of 6.0 mg/kg were 28.8 micrograms/ml and 24.6 micrograms/ml, and at a dose of 12.0 mg/kg were 65.4 micrograms/ml and 39.6 micrograms/ml, exhibiting a dose response. Plasma half lives in the beta phase were 0.97 and 1.20 hours at 6.0 mg/kg, and 0.72 and 0.94 hour at 12.0 mg/kg. Plasma concentrations determined by the HPLC method were lower than those determined by the bioassay. 3. Urinary excretion rates in the first 5.5 hours after the 6.0 mg/kg dose were 81.4 and 75.3%, and after the 12.0 mg/kg dose were 91.0 and 73.8%, and these values were higher than those obtained using HPLC. 4. Concentrations of L-627 in cerebrospinal fluid were determined in 2 cases of purulent meningitis. In one case, 30.3 mg/kg of L-627 was infused intravenously over 30 minutes and concentrations on days 1, 3, 7 and 14 observed at 60, 60, 45 and 45 minutes after respective dosages were 7.60, 1.30, 1.42 and 0.38 microgram/ml. Cerebrospinal fluid-plasma concentration ratio was determined on days 7 and 14 to be 5.5 and 1.2% respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

[Pharmacokinetic, bacteriological and clinical studies on cefozopran in the pediatric field].

Cefozopran (CZOP, SCE-2787), a newly developed parenteral cephem antibiotic, was administered to children with bacterial infections. We determined its antibacterial activity, pharmacokinetics, efficacy and safety in these patients. 1. Antibacterial activity MICs of cefmetazole, ceftazidime, cefuzonam, flomoxef and CZOP were determined against a total of 19 strains. For Gram-positive cocci, MICs of CZOP ranged from 0.39 to 0.78 microgram/ml against Staphylococcus aureus (3 strains), from 0.05 to 6.25 micrograms/ml against Streptococcus pneumoniae (5 strains), and 12.5 micrograms/ml against Enterococcus faecalis (1 strain). These MICs were generally similar to those of other cephems, but the MIC of CZOP against E. faecalis was lower than those of the other cephems examined. For Gram-negative bacilli, MICs of CZOP were 25 micrograms/ml against Citrobacter freundii (1 strain), and 6.25 micrograms/ml against Pseudomonas aeruginosa (1 strain). These values were similar to or lower than those of other cephems, MICs of CZOP against Haemophilus influenzae (7 strains) ranged from 0.1 to 0.39 microgram/ml. However, the MIC of CZOP against Serratia marcescens (1 strain) was higher than 100 micrograms/ml, and CZOP was as ineffective as the other cephems against this organism. 2. Pharmacokinetics CZOP was administered to children at 20 or 40 mg/kg via intravenous injection, and determinations were made for its serum concentrations, urinary concentrations and concentrations in cerebrospinal fluid (CSF) using the bioassay. Serum concentrations at 30 minutes after administration were 60.4 micrograms/ml with a dose of 20 mg/kg to one patient and 93.9 and 99.0 micrograms/ml with 40 mg/kg to two patients. The corresponding half-lives were 1.55 hours for 20 mg/kg administration, and 1.10 and 3.41 hours for 40 mg/kg, while the AUCs were 136.5 micrograms.hr/ml for 20 mg/kg, and 194.4 and 264.5 micrograms.hr/ml for 40 mg/kg. The rates of urinary recovery in the first 8 hours after administration were 45.0% in the patient receiving 20 mg/kg, and 84.6 and 97.6% in the two patients receiving 40 mg/kg. The concentrations in the CSF determined in 3 patients with purulent meningitis ranged from 2.6 to 16.0 micrograms/ml 1 hour after administration, and the CSF/serum concentration ratio ranged from 6.5 to 39.0%. These values for pharmacokinetic parameters obtained in the bioassay were similar to those obtained using HPLC. 3. Clinical evaluation Forty-eight patients were clinically evaluated. Of these patients, 75% were less than 3 years of age and there were slightly more male children than female children.(ABSTRACT TRUNCATED AT 400 WORDS)